This proposal is designed to investigate the significance of antiphospholipid antibodies (aPL) in ischemic stroke in the cohort of patients entered into the Warfarin Aspirin Recurrent Stroke Study (WARSS) project. aPL, seen in approximately 10% of first ischemic stroke patients may be a marker for increased risk of subsequent thrombo- occlusive events, including stroke. A unique opportunity has arisen to combine scientific interests of WARSS and the Antiphospholipid Antibodies in Stroke Study Group (APASS). WARSS is a randomized and double-blinded secondary stroke and death prevention trial comparing aspirin and warfarin in two treatment arms. The details of the WARSS/APASS collaboration have been worked out and will use mutually beneficial and highly cost-effective strategy to assess aPL status in all WARSS patients to test the hypothesis that a positive aPL status will confer a higher risk subsequent thrombo-occlusive events compared to WARSS patients who do not have aPL. APASS will obtain aPL status at baseline on all WARSS enrolled subjects and document all thrombo-occlusive events. aPL status will also be documented yearly and at the time of a recurrent thrombo-occlusive events for all aPL(+) patients and one matched aPL(-) patient for each aPL(+) patient to insure blinding of aPL status at each of the WARSS clinical centers. In addition, we believe that the important information obtained from this study could lead to a treatment trial potentially resulting in improved and more cost-effective health care for the subset of patients with stroke and aPL. This number is resulting in improved and more cost- effective health care for the subset of patients with stroke and aPL. This number is estimated to be at least 40,000 people per year in the United States. If we extrapolate from the prevalence data in a young stroke population alone, we can predict that there are probably almost 9,000 young people in the United States per year who suffer an episode of cerebral ischemia associated with aPL (500,000 new strokes per year with 4% occurring in people under the age of 50 and nearly 45% of these associated with aPL. As many as 1,260 of them will go on to develop recurrent stroke despite conventional therapy. The cost to care for these patients, just in terms of acute health care dollars spent, is over 30 million dollars, based on the Relative Index Scale. There are probably an additional 25,000 people over the age of 50 each year with aPL-associated stroke, increasing the potential "aPL" share of total stroke health care costs even more. One could extrapolate similarly for myocardial infarction, deep venous thrombosis, systemic thromboembolic events and fetal loss. The number of people in the United States per year (many of them less than 50 years of age) with this potentially treatable autoimmune-mediated syndrome is a major cause for concern and clearly demonstrates a need for further epidemiological study. There are benefits of linking APASS to WARSS, regardless of whether WARSS turns out to be a negative or a positive clinical trial for treatment differences. In addition, this an opportunity to pioneer a new level of collaborative effort with great potential to benefit stroke victims, contribute significantly to our basic knowledge about stroke mechanisms and save tax dollars.